HIV enters the central nervous system (CNS) very early after seroconversion. However, synaptic simplification, seen in HW-positive subjects, occurs in the late stage of infection. These abnormalities culminate in neurocognitive deficits termed HIV-associated neurocognitive disorder (HAND) or, the more severe form, HIV-associated dementia, even in the presence of the antiretroviral therapy. Symptoms include profound motor and behavioral/psychosocial abnormalities that negatively influence daily living.
Remarkably, HIV does not infect neurons, yet postmortem brains of subjects with HAD exhibit neuronal loss accompanied by synaptic simplification. Neurodegeneration seen in HIV positive subjects has been attributed to the combined effect of host cell-derived factors, including cytokines and glutamate and other neurotoxins produced by activated microglia/macrophages. In fact, HIV infection causes HIV encephalitis, which is characterized by neuroinflammation, astrogliosis and microgliosis, and results in an overall production and release of pro-apoptotic chemokines (e.g., interleukin-1β and tumor necrosis factor-α). However it is still unclear whether HIV, through viral proteins, can induce neuronal damage directly.
There are presently no therapies available for treating HAD. Thus, there is an acute need for developing adjunct therapies that can provide some measure of treating HIV-mediated neuronal degeneration.